Alterations in regional homogeneity and functional connectivity associated with cognitive impairment in patients with hypertension: a resting-state functional magnetic resonance imaging study.

Our study aims to investigate the alterations and diagnostic efficiency of regional homogeneity (ReHo) and functional connectivity (FC) in hypertension patients with cognitive impairment. A total of 62 hypertension patients with cognitive impairment (HTN-CI), 59 hypertension patients with normal cognition (HTN-NC), and 58 healthy controls (HCs) with rs-fMRI data were enrolled in this study. Univariate analysis (based on whole-brain ReHo and seed-based FC maps) was performed to observe brain regions with significant differences among the three groups. Multiple voxel pattern analysis (MVPA) was applied to evaluate the diagnostic accuracy in classifying HTN-CI from HTN-NC and HCs. Compared with the HCs and HTN-NC, HTN-CI exhibited decreased ReHo in the right caudate, left postcentral gyrus, posterior cingulate gyrus, insula, while increased ReHo in the left superior occipital gyrus and superior parietal gyrus. HTN-CI showed increased FC between seed regions (left posterior cingulate gyrus, insula, postcentral gyrus) with many specific brain regions. MVPA analysis (based on whole-brain ReHo and seed-based FC maps) displayed high classification ability in distinguishing HTN-CI from HTN-NC and HCs. The ReHo values (right caudate) and the FC values (left postcentral gyrus seed to left posterior cingulate gyrus) were positively correlated with the MoCA scores in HTN-CI. HTN-CI was associated with decreased ReHo and increased FC mainly in the left posterior cingulate gyrus, postcentral gyrus, insula compared to HTN-NC and HC. Besides, MVPA analysis yields excellent diagnostic accuracy in classifying HTN-CI from HTN-NC and HCs. The findings may contribute to unveiling the underlying neuropathological mechanism of HTN-CI.

Disrupted topological organization of functional brain networks is associated with cognitive impairment in hypertension patients: a resting-state fMRI study.

PURPOSE: To investigate the alterations of topological organization of the whole brain functional networks in hypertension patients with cognitive impairment (HTN-CI) and characterize its relationship with cognitive scores. METHODS: Fifty-seven hypertension patients with cognitive impairment and 59 hypertension patients with normal cognition (HTN-NC), and 49 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging. Graph theoretical analysis was used to investigate the altered topological organization of the functional brain networks. The global topological properties and nodal metrics were compared among the three groups. Network-based statistic (NBS) analysis was used to determine the connected subnetwork. The relationships between network metrics and cognitive scores were also characterized. RESULTS: HTN-CI patients exhibited significantly decreased global efficiency, lambda, and increased shortest path length when compared with HCs. In addition, both HTN-CI and HTN-NC groups exhibited altered nodal degree centrality and nodal efficiency in the right precentral gyrus. The disruptions of global network metrics (lambda, Lp) and the nodal metrics (degree centrality and nodal efficiency) in the right precentral gyrus were positively correlated with the MoCA scores in HTN-CI. NBS analysis demonstrated that decreased subnetwork connectivity was present both in the HTN-CI and HTN-NC groups, which were mainly involved in the default mode network, frontoparietal network, and cingulo-opercular network. CONCLUSION: This study demonstrated the alterations of topographical organization and subnetwork connectivity of functional brain networks in HTN-CI. In addition, the global and nodal network properties were correlated with cognitive scores, which may provide useful insights for the understanding of neuropsychological mechanisms underlying HTN-CI.

BMRMI Reduces Depressive Rumination Possibly through Improving Abnormal FC of Dorsal ACC.

Rumination is a common symptom of major depressive disorder (MDD) and has been characterized as a vulnerability factor for the onset or recurrence of MDD. However, the neurobiological mechanisms underlying rumination and appropriate treatment strategies remain unclear. In the current study, we used resting-state functional magnetic resonance imaging to investigate the effects of body-mind relaxation meditation induction (BMRMI) intervention in MDD with rumination. To this aim, we have recruited 25 MDD and 24 healthy controls (HCs). Changes in functional connectivity (FC) of the anterior cingulate cortex (ACC) subregion and the scores of clinical measurements were examined using correlation analysis. At baseline, MDD showed stronger FC between the right dorsal ACC (dACC) and right superior frontal gyrus than did the HC group. Compared to baseline, the HC group showed a significantly enhanced FC between the right dACC and right superior frontal gyrus, and the MDD group demonstrated a significantly weaker FC between the left dACC and right middle frontal gyrus (MFG) after the intervention. Furthermore, the FC between the right dACC and right superior frontal gyrus was positively associated with rumination scores across all participants at baseline. The above results indicate that BMRMI may regulate self-referential processing and cognitive function through modulating FC of the dACC in MDD with rumination.

A (3,8)-Connected Metal-Organic Framework with Bending Dicarboxylate Linkers for C2H2/CO2 Separation.

Herein, by replacement of the linear terephthalate linker with the bending 2,5-thiophenedicarboxylate (tdc2-) linker in the typical (3,9)-connected metal-organic framework, with a reduced 8-connected hydroxyl-centered trinuclear cluster, a new (3,8)-connected network, [Ni3(µ3-OH)(tdc)3(tpp)] [DZU-1; tpp = 2,4,6-tris(4-pyridyl)pyridine], was synthesized. The modified pore environment enables DZU-1 to selectively adsorb C2H2 over CO2 in an efficient manner.

Effect and neural mechanisms of the transcutaneous vagus nerve stimulation for relapse prevention in patients with remitted major depressive disorder: protocol for a longitudinal study.

INTRODUCTION: After the first episode, patients with remitted major depressive disorder (MDD) have a 60% chance of experiencing a second episode. There are currently no accepted, effective methods to prevent the recurrence of MDD in remission. Transcutaneous vagus nerve stimulation (taVNS) is a non-invasive, safe and economical approach based on the efficacy of VNS in improving clinical depression symptoms. This clinical trial will study the efficacy of taVNS in preventing MDD relapse and investigate the underlying mechanisms of this. METHODS AND ANALYSIS: We will conduct a multicentre, randomised, patient-blinded and evaluators double-blinded trial. We will randomise 90 eligible participants with recurrent MDD in remission in a 1:1 ratio into a real or sham taVNS group. All participants will be given six biopsychosocial assessments: proinflammatory cytokines, serum monoamine neurotransmitters, cognition, affective neuropsychology, multimodal neuroimaging and endocrinology. After the baseline measurements, all participants will be given corresponding interference for 6 months and then complete a 1-year follow-up. The assessments will be performed three times: at baseline, post-treatment and at the end of 1-year follow-up (except for multimodal MRI scanning, which will be conducted at the first two assessments only). Change in 17-item Hamilton Depression Rating Scale scores for MDD is the primary outcome parameter. ETHICS AND DISSEMINATION: The study protocol was approved by the Medical Ethical Committee of Beijing Hospital of Traditional Chinese Medicine on 18 January 2019 (2018BL-076). The trial results will be published in peer-reviewed journals and at conferences. TRIAL REGISTRATION NUMBER: ChiCTR1900022618.

Increased prefrontal cortex connectivity associated with depression vulnerability and relapse.

BACKGROUND: Major depressive disorder (MDD) is a highly prevalent mood disorder, characterized by depressed mood, reduced capabilities to concentrate, impaired cognition, as well as a high risk of relapse. Unaffected siblings who have high risks for MDD development and yet without clinical symptoms may be helpful for understanding the neural mechanisms of MDD traits. METHODS: We investigated both regional fluctuation and inter-regional synchronization in 31 fully remitted MDD patients, 29 unaffected siblings and 43 age, gender, and educational level matched helathy controls (HCs) using resting-state functional magnetic resonance imaging (rs-fMRI). The 17-item HAMD and neurocognitive scales were performed. Fractional amplitude of low-frequency fluctuation (fALFF) and functional connectivity (FC) strength were investigated. RESULTS: Compared with healthy control group, patients with remitted MDD and unaffected siblings showed increased fALFF in the left dorsomedial prefrontal cortex (dmPFC) and increased FC between the left dmPFC and the right ventromedial prefrontal cortex (vmPFC). In addition, a negative correlation was observed between the fALFF value in the left dmPFC and the speed of Trail Making Test in the remitted MDD patients. Higher vmPFC-dmPFC FC was positively correlated with Wisconsin Card Sorting Test (WCST) total correct, and negatively correlated with WCST random errors. CONCLUSIONS: In the absence of clinical symptoms, individuals with remitted MDD and unaffected siblings showed increased fALFF in left dmPFC as well as the vmPFC-dmPFC connectivity. These results suggest a specific trait abnormality in the default mode network associated with vulnerability to MDD, which may have implications for developing effective therapies using this network as a target.

Orf165 is associated with cytoplasmic male sterility in pepper.

Cytoplasmic male sterility (CMS) is a maternally inherited trait that derives from the inability to produce functional pollen in higher plants. CMS results from recombination of the mitochondrial genome. However, understanding of the molecular mechanism of CMS in pepper is limited. In this study, comparative transcriptomic analyses were performed using a near-isogenic CMS line 14A (CMS-14A) and a maintainer line 14B (ML-14B) as experimental materials. A total of 17,349 differentially expressed genes were detected between CMS-14A and ML-14B at the PMC meiosis stage. Among them, six unigenes associated with CMS and 108 unigenes involved in energy metabolism were identified. The gene orf165 was found in CMS-14A. When orf165 was introduced into ML-14B, almost 30% of transgenic plants were CMS. In addition, orf165 expression in transgenic CMS plants resulted in abnormal function of some genes involved in energy metabolism. When orf165 in transgenic CMS plant was silenced, the resulted orf165-silenced plant was male fertile and the expression patterns of some genes associated with energy metabolism were similar to ML-14B. Thus, we confirmed that orf165 influenced CMS in pepper.

Use of Transcutaneous Auricular Vagus Nerve Stimulation as an Adjuvant Therapy for the Depressive Symptoms of COVID-19: A Literature Review.

The coronavirus disease 2019 (COVID-19) comprises more than just severe acute respiratory syndrome. It also interacts with the cardiovascular, nervous, renal, and immune systems at multiple levels, increasing morbidity in patients with underlying cardiometabolic conditions and inducing myocardial injury or dysfunction. Transcutaneous auricular vagus nerve stimulation (taVNS), which is derived from auricular acupuncture, has become a popular therapy that is increasingly accessible to the general public in modern China. Here, we begin by outlining the historical background of taVNS, and then describe important links between dysfunction in proinflammatory cytokine release and related multiorgan damage in COVID-19. Furthermore, we emphasize the important relationships between proinflammatory cytokines and depressive symptoms. Finally, we discuss how taVNS improves immune function via the cholinergic anti-inflammatory pathway and modulates brain circuits via the hypothalamic-pituitary-adrenal axis, making taVNS an important treatment for depressive symptoms on post-COVID-19 sequelae. Our review suggests that the link between anti-inflammatory processes and brain circuits could be a potential target for treating COVID-19-related multiorgan damage, as well as depressive symptoms using taVNS.

Enhanced functional connectivity between insular subregions correlates with the efficacy of music and instruction-guided relaxation in depression.

Music and instruction-guided relaxation (MIGR) is a complementary therapeutic tool used in the treatment of the major depressive disorder (MDD). However, the neural mechanism that underlies the effect of MIGR on MDD patients is not known. Twenty-three right-handed MDD patients and 23 age-, sex-, handedness-, and educational level-matched healthy controls were enrolled. Resting-state functional MRI data were acquired from patients before and after MIGR and from healthy controls. The relationships between insular subregion-based functional connectivity and Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale (HAM-A), Automatic Thoughts Questionnaire, and Ruminative Responses Scale scores were examined. One-way analysis of variance exhibited significant differences among the three groups in functional connectivity between the left dorsal anterior insula (dAI) and left superior medial frontal gyrus (SMFG), left dAI and left precuneus, left posterior insula and left gyrus rectus, right ventral anterior insula (vAI) and left posterior cingulate cortex (PCC), right vAI and right inferior frontal gyrus (R-IFG). Further comparisons in regions of interest showed that MDD patients before MIGR showed decreased functional connectivity between the left dAI and left SMFG, left dAI and left precuneus, left posterior insula, and left gyrus rectus, right vAI and left PCC, right vAI and R-IFG relative to those in healthy controls. The strength of functional connectivity between the right dAI and left putamen also exhibited a negative correlation with the HAM-A score in MDD cases before MIGR. MIGR may result in enhanced functional connectivity in insular subregions, thereby potentially increasing the regulatory influence of cognitive reappraisal.

Risk Factor Analysis and Risk Prediction Model Construction of Pressure Injury in Critically Ill Patients with Cancer: A Retrospective Cohort Study in China.

BACKGROUND The aim of this study was to analyze the risk factors of pressure injury (PI) in critically ill patients with cancer to build a risk prediction model for PI. MATERIAL AND METHODS Between January 2018 and December 2019, a total of 486 critically ill patients with cancer were enrolled in the study. Univariate analysis and binary logistic regression analysis were used to explore risk factors. Then, a risk prediction equation was constructed and a receiver operator characteristic (ROC) curve analysis model was used for prediction. RESULTS Of the 486 critically ill patients with cancer, 15 patients developed PI. Risk factors found to have a significant impact on PI in critically ill patients with cancer included the APACHE II score (P<0.001), semi-reclining position (P=0.006), humid environment/moist skin (P<0.001), and edema (P<0.001). These 4 independent risk factors were used in the regression equation, and the risk prediction equation was constructed as Z=0.112×APACHE II score +2.549×semi-reclining position +2.757×moist skin +1.795×edema-9.086. From the ROC curve analysis, the area under the curve (AUC) was 0.938, sensitivity was 100.00%, specificity was 83.40%, and Youden index was 0.834. CONCLUSIONS The PI risk prediction model developed in this study has a high predictive value and provides a basis for PI prevention and treatment measures for critically ill patients with cancer.

Flower transcriptome dynamics during nectary development in pepper (Capsicum annuum L.).

The measurement of gene expression can provide important information about gene function and the molecular basis for developmental processes. We analyzed the transcriptomes at three different developmental stages of pepper flower [sporogenous cell division, stage (B1); pollen mother cell meiosis, stage (B2); and open flower (B3)]. In the cDNA libraries for B1, B2, and B3: 82718, 77061, and 91491 unigenes were assembled, respectively. A total of 34,445 unigene sequences and 128 pathways were annotated by KEGG pathway analysis. Several genes associated with nectar biosynthesis and nectary development were identified, and 8,955, 12,182, and 23,667 DEGs were identified in the B2 vs B1, B3 vs B1, and B3 vs. B2 comparisons. DEGs were involved in various metabolic processes, including flower development, nectar biosynthesis, and nectary development. According to the RNA-seq data, all 13 selected DEGs showed similar expression patterns after q-PCR analysis. Sucrose-phosphatase, galactinol-sucrose galactosyltransferase, and sucrose synthase played very important roles in nectar biosynthesis, and CRABS CLAW could potentially be involved in mediating nectary development. A significant number of simple sequence repeat and single nucleotide polymorphism markers were predicted in the Capsicum annuum sequences. The new results provide valuable genetic information about flower development in pepper.

CUDC-907 displays potent antitumor activity against human pancreatic adenocarcinoma in vitro and in vivo through inhibition of HDAC6 to downregulate c-Myc expression.

Pancreatic adenocarcinoma is a highly malignant cancer that often involves a deregulation of c-Myc. It has been shown that c-Myc plays a pivotal role in the regulation of a variety of physiological processes and is involved in early neoplastic development, resulting in poor progression. Hence, suppression of c-Myc overexpression is a potential strategy for pancreatic cancer therapy. CUDC-907 is a novel dual-acting inhibitor of phosphoinositide 3-kinase (PI3K) and histone deacetylase (HDAC). It has shown potential efficiency in patients with lymphoma, multiple myeloma, or thyroid cancer, as well as in solid tumors with c-Myc alterations, but the evidence is lacking for how CUDC-907 regulates c-Myc. In this study, we investigated the effect of CUDC-907 on human pancreatic cancer cells in vitro and in vivo. Our results showed that CUDC-907 potently inhibited the proliferation of 9 pancreatic cancer cell lines in vitro with IC50 values ranging from 6.7 to 54.5 nM. Furthermore, we revealed the antitumor mechanism of CUDC-907 in Aspc-1, PANC-1, and Capan-1 pancreatic cancer cells: it suppressed the HDAC6 subunit, thus downregulating c-Myc protein levels, which was a mode of action distinct from the existing mechanisms. Consistently, the extraordinary antitumor activity of CUDC-907 accompanied by downregulation of c-Myc and Ki67 expression in tumor tissue was observed in a human pancreatic cancer Aspc-1 xenograft nude mouse model in vivo. Our results suggest that CUDC-907 can be a valuable therapeutic option for treating pancreatic adenocarcinoma.

The flavonoid TL-2-8 induces cell death and immature mitophagy in breast cancer cells via abrogating the function of the AHA1/Hsp90 complex.

The flavonoid quercetin exhibits significant anticancer activities with few side effects. In the current study, we characterized TL-2-8, a quercetin derivative, as a novel anticancer agent in vitro and in vivo. Cell proliferation and viability were assessed using Cell Counting Kit-8 and CellTiter-Blue assay, respectively. Cell death was examined using PI staining or a TUNEL assay. Mitophagy was determined by measuring autophagic flux and by confocal imaging. Protein expression was examined by Western blotting. We found that TL-2-8 selectively inhibited the proliferation and decreased the viability of various cancer cells (the anti-proliferation IC50 values in MDA-MB-231, MDA-MB-468 and MCF-7 breast cancer cells at 72 h were 8.28, 8.56, and 9.58 µmol/L, respectively), and it displayed only slight cytotoxicity against normal MCF-10A and HEK-293 cells. In MDA-MB-231 and MDA-MB-468 breast cancer cells, TL-2-8 treatment induced the degradation of multiple Hsp90 client proteins without inducing Hsp70. TL-2-8 (3, 6, 12 µmol/L) dose-dependently inhibited the expression of AHA1, an activator of Hsp90 ATPase, and decreased Hsp90-AHA1 complex formation, leading to decreased Hsp90 chaperone function and reduced polo-like kinase 1 (PLK1) signaling. Consequently, impaired mitophagy was induced via the downregulation of lysosomal-associated membrane protein 2 (LAMP2). The in vivo anticancer effects of TL-2-8 were evaluated in an MDA-MB-231 breast cancer xenograft model, which was treated with TL-2-8 (25, 50, 100 mg·kg-1·d-1, po). Administration of TL-2-8 resulted in tumor growth inhibition rates of 37.9%, 58.9% and 70.9%, respectively, whereas quercetin treatment (100 mg·kg-1·d-1, po) produced only a lower tumor growth inhibition rate (49.5%). Furthermore, TL-2-8 treatment significantly extended the lifespan of mice bearing MDA-MB-231 breast cancer cell xenografts. Our results demonstrate that TL-2-8 induces significant cell death and immature mitophagy in breast cancer cells in vitro and in vivo via AHA1 abrogation.

Serum microRNA 143 and microRNA 215 as potential biomarkers for the diagnosis of chronic hepatitis and hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is regarded as one of the most common malignancies and among the leading causes of cancer death among the whole world. The most urgent needs are to find sensitive markers for early diagnosis or monitor postoperative recurrence and to give adequate treatment for HCC. MicroRNAs (miRNAs) are reported as a group of small non-coding RNAs that can function as endogenous RNA interference to regulate expression of the targeted genes. This study was conducted to detect the application of miR-143 and miR-215 in the diagnosis of HCC. METHODS: A total of 340 serum samples (127 samples from controls, 118 samples from hepatitis and 95 samples from HCC patients) were collected. The levels of the two mature miRNAs (miR-143 and miR-215) were detected by probe-based stem-loop quantitative reverse-transcriptase PCR (RT-qPCR) in controls, hepatitis and HCC patients. Besides, the relationship between miR-143 and miR-215 levels and clinical and pathological factors was explored. RESULTS: We found that the expression of serum miR-215 was distinctly increased in chronic hepatitis compared with controls (mean ± SD: 6.79 ± 0.72 vs. 3.46 ± 0.37, P < 0.001 and mean ± SD: 8.38 ± 0.87 vs. 3.46 ± 0.37, P < 0.001). In addition, we conduct ROC analyses to detect the potential application of miR-143 and miR-215 in the diagnosis of chronic hepatitis and HCC. Our results showed that miR-143 and miR-215 might be a potential biomarker for the hepatitis and HCC. CONCLUSIONS: In conclusion, the expression of miR-143 and miR-215 in serum were significantly up-regulated in patients with chronic hepatitis and HCC. Due to its reasonable sensitivity and specificity for both diseases, miR-143 and miR-215 could be as potential circulating biomarkers. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1048932281272754.

Photooxidation tolerance characters of a new purple pepper.

Huai Zi (HZ) is a new purple mutant of green pepper (PI 631133) that is obtained from the United States Department of Agriculture. The net photosynthetic rate (P N), chlorophyll fluorescence parameters, antioxidant substances, antioxidant enzymes, photosystem 1 (PS1) and PS2 activities were studied through methyl viologen (MV) treatment. The results showed that the P N, actual photochemical efficiency of PS2 (ΦPS2), photochemical quenching coefficient (qP), PS1 and PS2 activities in HZ were lower than those in green pepper. HZ had a stronger ability to eliminate reactive oxygen species(O2 (•-)) and accumulated less malondialdehyde (MDA) (a membrane lipid peroxidation product) than did green pepper, and had a higher content of antioxidants and antioxidant enzyme activity. This suggests that the lower light energy absorption and higher thermal dissipation and antioxidant activity of HZ contributed to a more stable PS2 photosynthetic capacity, which resulted in photooxidation tolerance. Hence, our study strongly suggests that pepper hybrids can achieve a modest ratio of chlorophyll and anthocyanin content, high P N and resistance to photooxidation, improving yield and resistance to adverse environments.